( T I T L E)ABSTRACT :Protein Tyrosine phosphatase an enzyme that is being present in staphylococcusinfection that plays an important role in cellular localization, enzyme stability. It follows signal transduction pathway, followed by an enzyme for cell cycle and MAP kinase pathway.
The enzyme tyrosine phosphatase contains two low molecular weight proteins like PtpA and PtpB that produce pathogenic staphylococcus infection.Most strains are resistant to penicillin and MRSA that are common in the hospitals and are emerging in the community.The staphylococcus infection mostly infects the skin and can be spread. The virulent infection had cause severe damage is Methicillin Resistant Staphylococcus aureus (MRSA) that have high pathogenicity causing infection that interchanging the nature from a drug to toxin character. Along with strain some coagulase negative bacteria is being produced like S.
aureus and S.endocarditis the interferes in the immune defences. There are 30 different types of infection caused by staph infection through both coagulase positive and negative strains, by which the staphylococcus have the ability to synthesize or secrete many factors that allow the bacteria to survive in host of bacterial cell. By characterizing the S.
aureus only three tyrosine phosphatase is known. A infected patient should be treated with methicillin, if he/she is resistant to methicillin, vancomycin will be introduced into the patient, rather than that ampicillin is also used to the staph infection. Some methods like surgical and oral treatment is being processed on the prospective conditions.The key characteristics of ( LMW-PTP ) is that it binds at the active site fold with the members of classical tyrosine and dual specificity phosphatases families. At certain stage the LMW-PTP fold is conserved in S.
aureus by synthesizing and cloning in expression vector. The unique features Of PtpA is that the loops are on the peripheral of the molecule while loop 2 is close to active site that cause difference in substrate recognition. The diagnosis of staph infection begins with attempting to culture the bacteria from an infected site at any area with pus or blisters should be cultured.To identify the infection, standard microbiological technique is followed that include a positive coagulase to identify the S.aureus and S.epidermidis which is hemolytic and non hemolytic staph respectively.identify the S.
aureus and S.epidermidis which is hemolytic and non hemolytic staph infection respectively.This review mainly covers the pathogenicity of bacteria and its inhibition and its mode of antibiotic control.
Introduction :Protein Tyrosine Phosphatase , an enzyme that forms phosphorylated tyrosineresidue on protein by removing phosphate group. It plays an important role in protein interactions, cellular localization, protein stability and regulate enzyme activity. Along with certain proteins like Ser/Thr, tyrosine phosphatases is associated with virulence and growth of pathogenic bacteria. The kinase mediated compounds is being controlled by phosphatases and makes the proteins to return to their unmodified state. ( Crystal structure of Protein Tyrosine Phosphatase 1B , Human )In signal transduction pathways, the regulatory components followed by the enzyme are for cell cycle control and MAP kinase pathway. Along with the signal transduction of tyrosine phosphatase it controls synaptic plasticity, transformation, differentiation, cell growth and proliferation. The enzyme Tyrosine Phosphatase that contains two low molecular weight proteins like PtpA and PtpB is being produced from the human pathogen Staphylococcus aureus.
The staphylococcus infection cause direct infection due to production of toxins by bacteria. Using cysteinyl-phosphate enzyme intermediate the tyrosine specific phosphatase catalyse the removal of phosphate group attached to tyrosine residue.In expression pattern, All cell types may express individual PTP,s ( Protein tyrosine phosphatases),30 to 60 % of cells mostly express all PTP,s. Some cells like hematopoietic and neural express PTP,s than other cells in high number, 60 to 70 different PTP,s express hematopoietic origin of T-cells and B-cells.Several PTP,s like PTPN5 is being restricted to brain for expressing. The reason for being restricted is that the PTPN5 that is found in many brain regions with different expressions but no expression in the cerebellum.
. Furthermore, it is being highlighted about the pathogenicity and the inhibitors of tyrosine phosphatases for staphylococcus infection and consequences.Pathogenicity in staphylococcus infection : Staphylococcus that have the ability to synthesize or secrete many factors thatallows bacteria to survive in the host or cause damage to host tissues. Staphylococcus bacteria which is a Gram-stain positive bacteria, and also find as either single or pair cells. It is genus bacteria that is in spheroid shape that resembles in bunch of grapes ( that appear in microscope after staining ). Coagulase ( an enzyme that can clot blood ) are separated by major divisions of genus staphylococcus.The staphylococcus infection mostly infect the skin and its structure, example: sebaceous gland, hair follicles. Sometimes these bacteria can reach in the blood stream that cause severe harm like wound infections, osteomyelitis,pneumonia.
These bacteria produce strains like Staphylococcus epidermidis and Staphylococcus aureus that are coagulase-negative produce slime that interferes with immune defences. Mainly S.aureus strains produce enzymes and toxins likely increase the severity of certain diseases like food poisoning, septic shock and scalded skin syndrome.
S.epidermidis strains usually can cause infections in people whose immune system is suppressed.Some signs of staph infections are 😕 Cellulitis :- It shows redness and swelling involved in the area without pus, but impetigo shows a crusty weeping rash with occasional blister.
? Scalded skin :- It shows the extensive skin redness with pus filled blisters.? Infected catheters :- Usually shows tenderness ,pus at skin entry site.The diagnosis of staph infection begins with attempting to culture the bacteria from an infected site at any area with pus or blisters should be cultured.To identify the infection, standard microbiological technique is followed that include a positive coagulase to identify the S.aureus and S.epidermidis which is hemolytic and non hemolytic staph respectively.identify the S.aureus and S.
epidermidis which is hemolytic and non hemolytic staph infection respectively. ( Beginning stage ) ( Last stage ) TABLE 1 : Toxins It’s causes Surface proteins Host immune cell’s ability to ingest and kill bacteria Membrane altering toxins Damage host cells by making holes in their membrane Exfoliatin toxins Cause scalded skin syndrome in infants Enterotoxins Cause nausea and vomiting associated with food poisoning Toxic shock syndrome toxin Occurs usually in females with tampons such as wound infection coagulase Possibly protects staph bacteria from host immune cells causing bacterial aggregation. These are the common toxic disease that is being commonly caused to many patients. There are 30 different types of staph infection in which S.aureus and S.epidermidis is commonly caused bacteria. Even there is two parameters of staphylococcus infection that is coagulase positive and coagulase negative strain bacteria that easily survived in dry conditions. The coagulase positive bacteria can easily survive in surface dry conditions, in which the chance of transmission in S.
aureus will be implicated. In community acquired infections the MRSA- Methicillin resistant Staphylococcus aureus has became a major cause of hospitality acquired infections. The coagulase negative bacteria such as S.epidermidis, S.saprophyticus, S.lugdunensis, S.
caprae and S.schleiferi are bacteria that predominantly implicated in uncomplicated lower genitourinary tract infection that mainly cause in suppressed immune system. The most common infection with methicillin resistant S.aureus that is highly limited and resistance to all the antibiotics that produce two low molecular weight Tyrosine phosphatase like ptpA and ptpB.
The ptpA and ptpB contains two similar group sequence with low molecular weight protein tyrosine phosphatases (LMW-PTP). The key characteristics of ( LMW-PTP ) is that it binds at the active site fold with the members of classical tyrosine and dual specificity phosphatases families. At certain stage the LMW-PTP fold is conserved in S.aureus by synthesizing and cloning in expression vector. The unique features Of PtpA is that the loops are on the peripheral of the molecule while loop 2 is close to active site that cause difference in substrate recognition. LMW-PTP regulation are structurally identical in PtpA in tyrosine residues that involved in human pointing a possible regulatory role in S.
aureus. To being characterizing the cellular function of S.aureus only three tyrosine phosphatase is being currently known in S.aureus the auto phosphorylating tyrosine kinase, the heat shock and the Acetyl-Mannosamine Dehydrogenase. Like this many strains and live cells of bacteria is being initiated to grow, by its rapid growth abundant cells. The staphylococcus has a nature of spreading from one place to another that produce proteins like protein tyrosine phosphatase that plays an important role in producing toxins along with bacteria that is virulent in nature. There are only few antibiotics that can control the staphylococcus infections name as methicillin and vancomycin that have abilities to relate acting as the drug resistant to the pathogenesis of the bacteria with various inhibitory concentrations. In other ways, the virulence factors like armamentarium in staph infection is very extensive in structural and secreted product.
The severe infections like MRSA is being classified in either hospital acquired or community acquired MRSA. The main symptoms that caused by HA-MRSA ( Hospital acquired- MRSA) is rash, headaches, fever, fatigue,chest pain etc. The symptoms of CA-MRSA ( community acquired -MRSA ) is infections caused in cut, scratched areas with painful bump form on skin.The Inhibitor factors of staphylococcus infection :As the staph infection is mainly caused by staphylococcus bacteria that often begins with little cuts which get infected by bacteria that look like honey yellow crusting on the skin.
It cause a severe disease in the humans and other animals by producing toxins that can be diagnosed by inhibiting the bacteria by using resistant inhibitors that can be able to stop or control the growth of bacteria. The staph infection can be inhibited by both surgical or antibiotic treatment.some resistant staph infection is tougher to treat like Methicillin Resistant Staphylococcus Aureus (MRSA), because it is use to be resistant in commonly resistant used antibiotics. The effective antibiotics that can act against staph, and also shown to be non-MRSA staph including Nafcillin, Cefazolin, Dicloxacillin, Clindamycin, Trimethoprim, Doxycycline.
In which some minor infection is treated by Bacitracin and the serious infections that are usually treated with two or more antibiotics MRSA infections are Vancomycin that is able to inhibit the various multiple drug resistant staph.Nafcillin : This drug is in the penicillin group of antibiotics that is used to treat many different types of infections caused by staph bacteria. This drug has high activity against penicillinase producing staphylococci. This drug is rarely used due its side effect caused like allergy, may act as resistant along with MRSA.
Cefazolin : Cefazolin the most frequently prescribed parenteral antibiotics that is being treated with Staphylococcus infection endocarditis, which results in very slow responding when treated with penicillin and that of methicillin that reduces the number of microorganisms in cardiac vegetation. Therefore it is being eradicate that cefazolin is being failure to eradicate S.aureus bacteremia and endocarditis.Dicloxacillin : This drug is recommended to treat infections suspected or proven that is caused by beta-lactamase producing bacteria. Dicloxacillin is used to treat mild to moderate staph infection, but can’t able to cure the severe diseases.Clindamycin : Clindamycin inhibits the infections caused by erythromycin-resistant staphylococci that express Inducible Clindamycin Resistance (ICR). It can’t able to act or inhibit the infection against other resistant staph pathogens.
Trimethoprim : To inhibit the severe MRSA- infection , trimethoprim or sulfamethoxazole plays an important role in inhibiting the pathogens. It is being studied that the MRSA infection id being cured or controlled by taking higher dose of TMP (Trimethoprim). TMP acts against through inhibition of dihydropteroate synthase and tetrahydrofolate reductase leading to impaired thymidine biosynthesis. As the dosage is higher the high content of thymidine in infected tissue may potentially lead to decreased activity of TMP and higher dose is necessary.This has the ability to inhibit the infections such as tenderness, induration, erythema and edema. As result when MRSA gets more resistant, the high dose of TMP drug can’t able to cure the infections of soft tissue infections caused by MRSA.
Above the following, most of the drugs have minimal drawbacks against the staph infection and some drugs are capable to tolerant the MRSA infection. Except these the most influencing bacteria that have the inhibition standard by its nature is vancomycin, Ampicillin and oxacillin that has the capability to inhibit the infected bacteria.Vancomycin :This drug is being demonstrated by utility of non-mammalian system named as Galleria mellonella for studying the pathogenicity and inhibition of staph infection. The drug vancomycin is being exposed to the clinical and laboratory strains that effectively results in the activation of antibiotic. So in most institutions vancomycin remains the first line of antibiotic for MRSA infection. The binding of vancomycin to the enzyme producing bacterial infection that prevents the cell wall synthesis of long polymers of N-acetylmuramic acid and N-acetylglucosamine the form the backbone strands of bacteria cell wall and it prevents to cross link the backbone polymers. In recent studies the drugs approved for curing MRSA infections are vancomycin, linezolid, oxacillin and ampicillin. Glycopeptide vancomycin has been regarded as to treat infections due to MRSA.
Where vancomycin is a glycopeptide antibiotic that is used for treatment of clostridium difficile diarrhea and staphylococcal enterocolitis. It is a bactericidal antibiotic that exerts its effect by preventing bacteria from forming cells.Vancomycin is specially is used for the infections for serious staph infections when penicillins and cephalosporins can’t be used. It treats the colon and small intestine causing staph infections.
The brand name of vancomycin is Vancocin that kills the bacteria and prevent growth. It inhibits the formations between the enzymes involved in peptidoglycan synthesis. Vancomycin continues to be the drug of choice for treating most MRSA infections causes by multidrug resistant strain. Clindamycin or minocycline may be useful when patients do not have life-threatening infections caused by strains susceptible to these agents. At certain stage vancomycin may also be changed to toxic by Vancomycin Resistant Staphylococcus aureus ( VRSA) due to antimicrobial activities that changes the behavior of the antibiotic, due to resistant nature of staph infection.
As a result the vancomycin antibiotic will be able to tolerate the bacteria at minimal time of infection.Ampicillin :Ampicillin is a penicillin Beta-lactam antibiotic that used for the treatment for several gram positive bacteria. Ampicillin gave the promising result that have the tolerance level to control the activity of bacteria.This antibiotics inhibits the function of cell wall penicillin binding proteins.
Ampicillin antibiotic that contains Beta-lactam is infective to Penicillin Binding Protein ( PBP 2a ) used by MRSA that performs cell wall cross linking functions. At most aspects ampicillin plays an important role that is resistant to staph infection than other antibiotics. In recent survey it is being proved that the antibiotic ampicillin is more resistant and less sensitive by performing individual blood test. Another drug named as oxacillin also played the same role.
Oxacillin :This bacteria mainly inhibits the third and final stage of cell wall synthesis that is binding to penicillin resistant protein inside the host of bacterial cell wall. This antibiotic also comes under the class of Beta-lactam. Some staph infection may be oxacillin resistant as like methicillin resistant.
But at preferable conditions like when the infection gets to early stages this drug helps to inhibit the infection.CONSEQUENCES IN ANTIBIOTICS :There are many antibiotics that is being used for inhibiting the bacterial staphylococcus infection, at various stages. The main aspect is to inject the antibiotic into the bacterial host that mainly synthesize the cell wall functioning of binding proteins.
The bacteria contains protein tyrosine phosphatases and penicillin binding proteins that makes the drugs to resistant themselves . Some drug resistant bacteria like Methicillin Resistant Staphylococcus Aureus ( MRSA), VancomycinRresistant Staphylococcus Aureus (VRSA) and Oxacillin Resistant Staphylococcus Aureus (ORSA) are some infection causing bacteria that can’t be treated with respective drugs. Among these the antibiotic like ampicillin that has the capability to inhibit the infection and is mainly resistant to the MRSA. The study of dosage given to bacterial cell host should be control if the level of the dosage will be high it will be toxic. The enzyme protein tyrosine phosphatase that produces both Ptp A and Ptp B have low molecular weight with conserved forms. More serious staphylococcal infections like infection of bloodstream, pneumonia and endocarditis require culturing of samples of blood or infected body fluids or tissues. Laboratory is being established to diagnosis and perform special test to determine which antibiotics are effective against bacteria. Some minor infections is treated with triple antibiotic mixture of ointment and additionally in severe conditions they are surgically drained.
CONCLUSION :In this staph infection it is able to identify various types of resistant disease that is caused by different strains like MRSA,VRSA and ORSA. To overcome these disease we should have to follow microbial techniques to culture it and then initiate the drugs into it to treat the bacterial cell. Many antibiotics is being used to control the growth of staph infection causing bacteria, among some of the drugs becomes resistant to drugs like Methicillin, vancomycin that is being resistant like MRSA, VRSA respectively. To overcome these disease the antibiotic like Ampicillin that contains Beta-lactam is used, which plays an important role to control the growth of bacteria that cross links the cell wall functioning.
Staphylococcus that have the ability to synthesize or secrete many factors that allows bacteria to survive in the host or cause damage to host tissues, so that when the inhibitor is injected it will bind to the penicillin binding protein site to inhibit the process.